Particle size matters: diagnostics and treatment of small airways involvement in asthma.
Eur Respir J. 2010 Jul 1 Cohen J, Postma DS, Douma WR, Vonk JM, De Boer AH, Ten Hacken NH. University Medical Center Groningen, University of Groningen PO Box 30001, 9700 RB Groningen the Netherlands.
Small airways are an important site of inflammation and obstruction in asthma, which contributes to the severity of airway hyperresponsiveness (AHR) that is usually measured by nebulisation of large-particle stimuli. We investigated whether small and large particle sizes of aerosolized adenosine-'5-monophospate (AMP) provide similar severity of AHR. Additionally, effects of small-particle ICS ciclesonide and large-particle ICS fluticasone on AHR to large- and small-particle size AMP were assessed. After a 4-week run-in period using open-label fluticasone 100 mug b.i.d., 37 mild-to-moderate asthmatics underwent provocations with standard size (3.7 micron), large-particle (9.9 micron) and small-particle (1.06 micron) AMP. Subjects received 4-week ciclesonide 160 mug s.i.d. or fluticasone 100 mug b.i.d. (double-blind, double-dummy) followed by large- and small-particle AMP provocation. Small-particle AMP induced a 20% fall in FEV1 (PC20) at a significantly higher dose than large-particle AMP. Ciclesonide and fluticasone had comparable effects on AMP provocations. Not all subjects reached a PC20 at the highest AMP dose. In those who did, ciclesonide improved small-particle PC20AMP by 1.74 doubling doses (DD) (p=0.03), whereas fluticasone did not. Conversely, fluticasone improved large-particle PC20AMP significantly (1.32DD, p=0.03), whereas ciclesonide did not. Small-particle AMP provocation appears a promising tool to assess changes in small airways inflammation.
Future adjustments are necessary taking into account the very small-particle size used, with large exhaled fractions. In asthmatics reaching a PC20 with small- and large-particle AMP provocations, ciclesonide improves hyperresponsiveness with small-particle size AMP, and fluticasone with large-particle size. This warrants further research to target provocations and treatment to specific airway sizes.